This new investigator R21 is submitted in response to NIDA/NIMH PA-06-298. Experimentation with alcohol and drugs has been shown to be normative in adolescence, yet a notable proportion of youth persist beyond experimentation to develop significant problems. Recent work has identified groups of youth at increased risk, however the biobehavioral mechanisms that underlie the development of substance misuse remain unknown. One factor that may influence development of problematic substance use in adolescence is the youth's ability to make adaptive decisions based on information about the rewards and consequences associated with use. The proposed study will employ a cross-sectional design using structural equation modeling to evaluate the relationship between individual differences in behavioral and physiologic responsiveness to reward and punishment cues, and problematic substance use. We will recruit a community sample of 150 youth, as this will allow for recruitment of youth with a broader range of substance use relative to youth from forensic or treatment settings, and maximize generalizability of findings. Responsivity to reward and punishment cues will be measured by: 1) performance on a series of behavioral response tasks that assess behavioral control under conditions of reward alone, punishment alone, and mixed incentives, and 2) skin conductance responses to reward and punishment cues during these tasks. We believe that abnormal physiologic responsiveness to reward and punishment cues may confer liability to substance misuse by interfering with the youth's ability to use these cues to inform behavior. Further, we hypothesize that problematic use will be related explicitly to deficits in performance on tasks that require simultaneous consideration of rewards and consequences, much like real- world decision making regarding substance use. A study of this kind is important, as it will help identify the biobehavioral mechanisms responsible for substance use problems, and thus, in turn facilitate development of intervention strategies that more specifically target the unique processes involved in this pathway to substance misuse. Additionally, focus on adolescents allows examination of these mechanisms at a point more proximal to the onset of substance use and related problems, providing a clearer picture of their relationship and the opportunity to study behaviors while they are relatively new and potentially more amenable to change. A better understanding of specific biobehavioral risk mechanisms for problematic substance use will provide an empirical basis for designing more effective prevention and treatment programs. This is an especially important area of study for adolescents, as it is during adolescence that youth experiment with new behaviors, and as such, a deficit in responsiveness to environmental contingencies may interfere with the development of appropriate behavioral patterns, thus leading to more intransigent problems. Hence, examination of these risk mechanisms during adolescence, when use behaviors are acquired, might both better inform interventions and reduce the public health impact associated with chronic substance-related problems. [unreadable] [unreadable] [unreadable]